Structure of the Short-Form ATP-phosphoribosyltransferase from Acinetobacter Baumannii Reveals the Presence of a Novel Mg2+ Sequestering and Storage Site

Adenosine triphosphate phosphoribosyltransferase (ATP-PRT), a member of the phosphoribosyltransferase (PRT) superfamily of enzymes, catalyses the first step in the histidine biosynthesis pathway, which involves the nucleophilic substitution of ATP onto phosphoribosyl pyrophosphate (PRPP) to generate phosphoribosyl-ATP (PR-ATP) and pyrophosphate (PPi). The three-dimensional structure of short-form ATP-PRT from Acinetobacter baumannii (AbHisGS) was determined using the X-ray crystallographic method. The structure determination revealed two crystallographically independent molecules in the asymmetric unit that formed an antiparallel homodimer. In all the structures of HisGS proteins reported so far, the N-terminal segment is either absent from the amino acid sequence or not observed in the structure. This is the first structure where the N-terminal segment has been clearly observed. However, the most remarkable observation pertains to observing a Mg2+ ion in the structure with the help of the N-terminal segment, which is loosely held with six coordination linkages, out of which one contact is made to the carbonyl oxygen atom of Asn16 at an average distance of 2.06 Å, and the other five contacts were with water oxygen atoms at distances varying from 2.40 to 2.59 Å. All the coordinating water oxygen atoms were held in place by multiple hydrogen bonds from surrounding protein atoms. The relatively loose coordination environment of the Mg2+ ion indicates temporary sequestration of Mg2+, which may be released during catalytic need.